Neurometabolic Remodeling in Chronic Hiv Infection: a Five-Year Follow-up Multi-Voxel Mrs Study

Abstract

There is a lack of data about the long-term follow-up changes in neurometabolic profile and neuropsychological performance of HIV-positive subjects under continuous antiretroviral therapy (cART). The aim of the study was to assess changes in neurometabolic profile in chronically-infected, HIV-positive subjects during a five-year follow-up period, using multi-voxel proton magnetic resonance spectroscopy (1H-MRS). Nineteen neurologically asymptomatic, aviremic, HIV-positive subjects, underwent multi-voxel 2D MRS on a 3 T MR unit and synchronous neurocognitive assessment in a five-year follow-up period. Twelve voxels were placed in prefrontal cortices, anterior and posterior cingulate gyrus, intraparietal sulci, and frontal centrum semiovale white matter, to identify peaks of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myoinositol (mI). Ratios of NAA/Cr, NAA/Cho, NAA/mI, mI/Cr, and Cho/Cr were analyzed. Longitudinal differences in ratios and neurocognitive scores were tested with the Wilcoxon signed-rank-test. Statistical significance was set at p ≤ 0.004 significant, and 0.05 > p > 0.004 trending toward significance. A significant longitudinal increase in NAA/Cr ratio was observed in 5/12 voxels, while there was a trend toward significance in an additional three. The increase in Cho/Cr reached statistical significance in one voxel. Changes in the mI/Cr ratio demonstrated a significant increase in 4/12 voxels. A progressive increase in NAA/Cr, followed by better neurocognitive performance, may be an indicator of brain plasticity in the setting of chronic HIV-related neuronal injury. A progressive mI/Cr increase could be partly explained by glial proliferation due to functional compartment remodeling and partly attributable to insufficient control of persistent neuroinflammation by cART.

A longitudinal study of the brain structure network changes in HIV patients with ANI: combined VBM with SCN

“…This suggests the possibility of neuronal remodeling occurring in the context of ongoing inflammation and gliocyte proliferation. A five-year follow-up analysis on the brain function of patients lent support to this hypothesis (46), revealing neuronal remodeling in specific pathways related to attention/working memory, delayed recall, and language recognition, aligning with our current findings. This could be closely tied to functional reorganization induced by the brain injury.…”

Cingulate transcranial direct current stimulation in adults with HIV

“…The selection of ACC as the primary target region was motivated by a neural model of HAND we recently proposed [ 17 ], which recognizes ACC as one of the most commonly affected brain regions in PWH and proposes an important role of ACC injury in HAND progression—suggesting that the ACC may serve as a potential therapeutic target for HAND intervention and/or treatment. The important role of ACC in HIV brain disease is supported by neurobehavioral and brain imaging studies in HIV: first, ACC injury in PWH has been detected using various brain imaging techniques, including structural MRI [ 17 ], task-based functional MRI (fMRI) [ 18 ], task-free fMRI [ 19 ] and perfusion MRI [ 20 ], proton magnetic resonance spectroscopy (MRS) [ 3 , 21 – 23 ], and positron emission tomography (PET) [ 20 , 24 ]; second, the high prevalence of executive deficits [ 25 ] and apathy [ 26 ]—both are known to involve the ACC [ 27 – 29 ]—provides additional evidence supporting the prevalence and importance of ACC injury in PWH. Furthermore, using invasive and non-invasive brain stimulation techniques (including deep brain stimulation, repetitive transcranial magnetic stimulation (rTMS), and tDCS), previous studies provided evidence suggesting that dACC stimulation might be effective in modulating brain/cognitive function [ 30 – 33 ] and emotional processes [ 34 ], as well as in treating disorders like obsessive compulsive disorder [ 35 , 36 ].…”

Low Tissue Creatine: A Therapeutic Target in Clinical Nutrition

“…Interestingly, it appears that a reduction in myocardial creatine significantly correlates with the clinical severity of heart failure [ 24 ], with tissue creatine put forward as an independent multivariate predictor of cardiovascular mortality in patients with failing hearts [ 25 , 26 ]. Tissue creatine levels were also diminished in the skeletal muscle and brain of patients with chronic respiratory failure [ 27 , 28 ], extracts from lung cancer patients [ 29 ], pancreatic parenchyma in patients with adenocarcinoma [ 30 ], in the brain of patients with hepatitis C and chronic HIV infection [ 31 , 32 ], and in the thalamus of infants with malnutrition [ 33 ], while suboptimal creatine levels are suggested in chronic kidney disease [ 34 ], and preterm birth [ 35 ]. Although the causes of the above conditions are different, they all share a disease-associated creatine deficit.…”